Multi-sequence non-contrast MRI characterization of deep vein thrombosis in man
Alkystis Phinikaridou1, Prakash Saha2, Marcelo Andia3, Alberto Smith2, and René M Botnar1

1Biomedical Engineering, King's College London, London, United Kingdom, 2Academic Surgery, King's College London, London, United Kingdom, 3Radiology, Pontificia Universidad Católica de Chile, Santiago, Chile

Synopsis

Deep vein thrombosis (DVT) affects 1 in 1000 people. Its sequelae include post-thrombotic syndrome (PTS), which affects up to 75% of patients within 5 years and is characterised by persistent pain, swelling and ulceration. Thrombolysis can reduce PTS by a third and is attempted in patients with an ilio-femoral DVT and symptom onset of <3weeks. Determining age and thrombus structure by history alone is, however, subjective and there are no established methods to quantify the abundance of matrix proteins, which determines the response to lysis. This treatment is therefore only effective in ~60% of patients, which may unnecessarily exposes to haemorrhagic side effects. We have developed a non-contrast enhanced magnetic resonance, multi-sequence thrombus imaging (MSTI) technique that can provide information about the structural composition of experimental thrombus [1-2]. Here, we aim in translating the MRI approach into man and determine whether it can help guide venous intervention.

Introduction

Deep vein thrombosis (DVT) remains an important medical condition. The biophysical characteristics of thrombus may determine the response to endovascular interventions including lysis. We demonstrated that multi-sequence thrombus imaging (MSTI) using magnetization transfer (MT), apparent diffusion coefficient (ADC), and T1 mapping can characterize thrombus organization and identify thrombi amenable to thrombolysis in a murine model [1,2]. Here, we investigate whether MSTI can be translated to man and how these measurements associate with the outcome of intervention.

Methods

MSTI was performed in patients (n=6, male=3, female=3, age=28-46 years old) with ilio-femoral DVT undergoing lysis at 3T using a 32-channel coil. T2-prepared, bSSFP MR venography (MRV) was acquired with: TR/TE=4.2/2.1ms, flip angle=70º, FOV=220x299x200mm, matrix=112x148, slice thickness=2mm, resolution=2x2mm, averages=1, T2-prep-echo-time=30ms. 3D T1-weighted spoiled-GRE images were acquired with and without an on-resonance MT pre-pulse with: TR/TE=69/2.2ms, flip angle=18º, FOV=220x299x198mm, matrix=112x148, slice thickness=6mm, resolution=2x2mm, averages=1. The binomial-block MT pre-pulse had a duration=1.92ms and repetitions=1. 2D diffusion weighted spin-echo images were acquired with: TR/TE=1780/82ms, flip angle=90º, diffusion-echo-time=333ms, FOV=220x299x125mm, matrix=112x148, slice thickness=10mm, resolution=2x2mm, averages=2 and b-values=0, 333, 667, 1000 mm2/s. A 2D MOdified Look-Locker Inversion Recovery (MOLLI; 3-3-5) sequence was used for T1 mapping: TR/TE=3.3/1.6ms, flip angle=35°. FOV=220x299x198mm, matrix=112x148, slice thickness=6mm, resolution=2x2mm, averages=1. Thrombi were segmented on all images using Osirix and the T1, %MTR/cm3, and ADC values were reported.

Results

MSTI is feasible in man and successful characterization of ilio-femoral DVT was achieved in 30min. Two examples of DVT with different compositional MRI signature that responded differentially to 24h of lytic treatment are illustrated in Figures 1&2. Case 1: Balanced SSFP MR venography (MRV) shows an occlusive, hypointense, filling defect in both the Ieft external iliac vein (EIV) and common femoral vein (CFV) (Fig. 1A-B and 1D-E). MSTI shows that the thrombus in the left EIV (Fig. 1C) and CFV (Fig. 1F) has a short T1 relaxation time due to a high methaemoglobin concentration, low %MTR/cm3 suggestive of a loose fibrin network and low ADC values indicative of restricted water mobility between the blood cells and fibrin meshwork. Based on our pre-clinical data [1,2] we predicted that this thrombus would likely lyse after treatment. In fact, 24hrs after catheter directed thrombolysis (CDT), venography revealed a fully patent venous system (Fig. 1G). Case 2: SSFP MR venography shows a central hypointense thrombus in the left EIV (Fig. 2A-B) and CFV (Fig. 2D-E) surrounded by a peri-thrombus region of high signal intensity due to vein wall oedema. MSTI shows a long T1 relaxation time (low methaemoglobin content), high %MTR/cm3 (dense collagen concentration) and high ADC (less restricted mobility of water molecules within the thrombus) in both the left EIV and CFV (Fig. 2C and 2F). These MRI findings suggest that the thrombus is acellular and collagen-rich and mostly likely unresponsive to lysis. 24h following CDT, venography (Fig. 2G1-G2) demonstrated no response to lytic therapy. In this case, MSTI assessment of thrombus composition may have prevented the unnecessary exposure of the patient to the haemorrhagic risks associated with catheter directed thrombolysis. Quantitative MRI data show the potential of MTR, ADC and T1 mapping in detecting compositional differences in DVT that could be predictive of the outcome of thrombolytic treatment (Fig. 3).

Conclusions

Non-contrast MSTI, using a combination of MTR, ADC and T1 mapping is feasible in man and may allow characterization of thrombus composition and understanding on how these measurements relate to the outcome of interventions.

Acknowledgements

British Heart Foundation (RG/12/1/29262 & PG/08/0392/24436)

FONDECYT 1130379

References

1. Saha P., et al. Circulation (2013).

2. Phinikaridou A., et al. Circulation; Cardiovasc Imaging (2013).

Figures

Figure 1: MSTI of an occlusive thrombotic-acute iliofemoral DVT and the outcome of therapy.

Figure 2: MSTI of an occlusive post-thrombotic (chronic) iliofemoral DVT that was not susceptible to thrombolytic therapy.

Figure 3: Quantitative analysis of the MRI data. There are compositional differences between thrombus that lyse and those that do not lyse after 24hr of lytic treatment in man.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
1115